Plasma exchange in kidney transplantation: Still a valuable option for nephrotic syndrome recurrence.

About 30% of the cases of steroid resistant nephrotic syndrome display a genetically determined disease and will not recur after kidney transplant; the other cases with fully or partially immunological pathogenesis display a high risk of post transplant recurrence. Although lots of studies were carried out in the last 50 years the pathogenetic mechanism is still obscure and the therapeutic approach mostly empirical. The cornerstones principles of the therapies are based on removal of a still undefined "permeability factor" through plasma-exchange or other apheresis techniques and inhibition of its synthesis by the immunological system through different drugs. The probability of successfully inducing persistant remission is nowadays around 30%through the different schemes experimented so far which mostly include plasmapheresis. Rituximab in the last years has significantly increased the efficacy of the treatments. Non responders are rapidly evolving to graft loss and will most probably recur also in subsequent transplant. Apart from genetics no other risk factors are predictive for recurrence.

Extracorporeal photopheresis for graft-versus-host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome-results from a large single-center study.

BACKGROUND: Extracorporeal photopheresis (ECP) has been shown as active therapy for graft-versus-host disease (GVHD). STUDY DESIGN AND METHODS: The aim was to ascertain the role of ECP in 71 patients with steroid-refractory or -dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD. RESULTS: The overall response rate (ORR) for aGVHD was 65% and the complete aGVHD-free survival was 50% (95% confidence interval [CI], 36%-70%). The ORR for cGVHD response was 81% while the complete cGVHD-free survival was 50% (95% CI, 34%-73%). The aGVHD-free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD-free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant-related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively. CONCLUSIONS: While confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response.

Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report.

This study was aimed at ascertaining whether extracorporeal photopheresis (ECP) is an effective treatment for pediatric patients with steroid resistant graft versus host disease (GvHD). Fifteen patients with acute GvHD (aGvHD) and 10 patients with chronic GvHD (cGvHD) were enrolled in the study. At the start of the ECP protocol, aGvHD was staged as II (n=7), III (n=4), and IV (n=4). The response rate was 100% for aGvHD II, 75% for aGvHD III, and finally 0% for aGvHD IV (P=0.02). In multivariate analysis, the strongest predictor for ECP response was the aGvHD severity: aGvHD II 100%, aGvHD III-IV 30% [relative risk (RR) 5.071, confidence interval (CI) 95% 2.2-5.5, P=0.0016], this translates in a higher risk of transplant-related mortality for ECP nonresponders (RR 5.26, CI 95% 3.4-6.2, P=0.02). cGvHD was diagnosed as limited n=3, and extensive n=7; the response rate was 100% and 28% for limited or extensive cGvHD, respectively (P=0.03). For cGvHD the strongest predictor for ECP response was the absence of visceral organ involvement (RR 5.17, CI 95% 2-4.9, P=0.001), and the highest risk of transplant-related mortality was among patients not responding to ECP (RR 12.4, CI 95%, P=0.02). Our results suggest that ECP can rescue good-risk GvHD-patients, whereas for advanced, poor-risk GvHD patients, new therapies are required.

Recovery of cord blood hematopoietic progenitors after successive freezing and thawing procedures.

BACKGROUND AND OBJECTIVES: Cord blood (CB) is a valuable source of stem cells. Most CB units are still cryopreserved in single bags in the world's CB banks. Thawing a single CB unit, dividing it into two parts, expanding the smaller one and refreezing the other would optimize ex vivo expansion of CB progenitors prior to transplantation: expanded and unexpanded cells could be infused together to accelerate early engraftment. DESIGN AND METHODS: The feasibility of refreezing CB samples was investigated by evaluating the effect of 3 successive cryopreservation procedures in 9 CB units. The number and viability of WBC, BFU-E, CFU-GM, CFU-MIX, LTC-IC, and the absolute CD34+ cell count were assessed at time 0 and after each thawing. The percentage of CD34 cells expressing CD38, L-selectin, VLA-4, VLA-5, H-CAM, LFA-1 and CXCR4 was also evaluated. RESULTS: After three freezing and thawing procedures, WBC counts decreased, while lymphocytes were unchanged. Viability was 90% of basal values after the first thawing and did not change. BFU-E decreased significantly only after the third thawing. CFU-GM and CFU-MIX did not change significantly, nor did LTC-IC, CD34+ cell counts and CAM and CXCR4 expression on CD34+/ CD38-- cells. INTERPRETATION AND CONCLUSIONS: These data show that two successive freeze-thaw procedures do not significantly affect the clonogenic potential and CAM expression of cord blood progenitors. This information could be exploited to devise new options in ex vivo expansion procedures and quality controls prior to transplantation.